Growth factor inhibitors have been used to treat many cancers including pancreatic, breast, lung and colorectal cancers. However, resistance to growth factor inhibitors has emerged as a significant clinical problem.
Tumor resistance to targeted therapies occurs due to a combination of stochastic and instructional mechanisms. Mutation/amplification in tyrosine kinase receptors or their downstream effectors account for the resistance of a broad range of tumors. In particular, oncogenic KRAS, the most commonly mutated oncogene in human cancer, has been linked to EGFR inhibitor resistance. However, in lung and pancreatic carcinomas, recent studies suggest that oncogenic KRAS is not sufficient to account for EGFR inhibitor resistance indicating that other factor(s) might control this process.